A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17.

Mutations in the microtubule-associated tau gene are responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). A reduced ability of the mutated microtubule-associated tau protein to interact with microtubules causes microtubule destabilization leading to deleterious effects on axonal transport and the formation of tau filaments. Here, we describe a new mutation of the tau gene, a T --> C transition at position +11 of the intron following exon 10 (T --> C 3'E10 +11) in the family showing frontotemporal dementia with very early age of onset (the first decade of proband's life). The T -->C 3'E10 +11 mutation caused a large increase in the proportion of transcripts containing exon 10 detected by exon-trapping analysis. Our study confirmed that the T --> C 3'E10 +11 mutation, as the other 5' splice site mutations of tau exon 10, modifies alternative splicing of exon 10.